Ann Pediatr Endocrinol Metab.  2016 Mar;21(1):21-25. 10.6065/apem.2016.21.1.21.

Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density

• Lim SW
• Ahn JH
• Choi A
• Cho WH
• Lee JA
• Kim DH
• Seo JH
• Lim JS

• KMID: 2161302
• DOI: http://doi.org/10.6065/apem.2016.21.1.21

Abstract

PURPOSE
Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients.
METHODS
Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated.
RESULTS
After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm2 after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia.
CONCLUSION
Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

Keyword

Child; Osteosarcoma; Pamidronate; Bone mineral density

MeSH Terms

Absorptiometry, Photon
Acute-Phase Reaction
Bone Density*
Child
Drug Therapy
Fractures, Spontaneous
Humans
Hypocalcemia
Osteoporosis
Osteosarcoma*
Spine

Figure

• 

  Fig. 1 The lumbar spine bone mineral density changes after pamidronate treatment. (A) Changes in bone mineral density lumbar spine (BMDLS mg/cm2) of osteosarcoma patients (P2 to P9, case 2 to 9) at baseline and after follow-up. (B) Changes in the BMDLS z-scores of osteosarcoma patients. The interval from first BMDLS evaluation to next BMDLS evaluation was 8.4±1.0 months.

Reference

1. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009; 152:3–13. PMID: 20213383.

2. Holzer G, Krepler P, Koschat MA, Grampp S, Dominkus M, Kotz R. Bone mineral density in long-term survivors of highly malignant osteosarcoma. J Bone Joint Surg Br. 2003; 85:231–237. PMID: 12678358.

3. Lim JS, Kim DH, Lee JA, Kim DH, Cho J, Cho WH, et al. Young age at diagnosis, male sex, and decreased lean mass are risk factors of osteoporosis in long-term survivors of osteosarcoma. J Pediatr Hematol Oncol. 2013; 35:54–60. PMID: 23128330.

4. Ahn JH, Cho WH, Lee JA, Kim DH, Seo JH, Lim JS. Bone mineral density change during adjuvant chemotherapy in pediatric osteosarcoma. Ann Pediatr Endocrinol Metab. 2015; 20:150–154. PMID: 26512351.

5. Pirker-Fruhauf UM, Friesenbichler J, Urban EC, Obermayer-Pietsch B, Leithner A. Osteoporosis in children and young adults: a late effect after chemotherapy for bone sarcoma. Clin Orthop Relat Res. 2012; 470:2874–2885. PMID: 22806259.

6. Hortobagyi GN, Theriault RL, Lipton A, Porter L, Blayney D, Sinoff C, et al. Protocol 19 Aredia Breast Cancer Study Group. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol. 1998; 16:2038–2044. PMID: 9626201.

7. Terpos E, Berenson J, Cook RJ, Lipton A, Coleman RE. Prognostic variables for survival and skeletal complications in patients with multiple myeloma osteolytic bone disease. Leukemia. 2010; 24:1043–1049. PMID: 20376081.

8. Srivastava T, Alon US. The role of bisphosphonates in diseases of childhood. Eur J Pediatr. 2003; 162:735–751. PMID: 14523647.

9. Sebestyen JF, Srivastava T, Alon US. Bisphosphonates use in children. Clin Pediatr (Phila). 2012; 51:1011–1024. PMID: 22935217.

10. Sonnemann J, Eckervogt V, Truckenbrod B, Boos J, Winkelmann W, van Valen F. The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro. Anticancer Drugs. 2001; 12:459–465. PMID: 11395574.

11. Ory B, Heymann MF, Kamijo A, Gouin F, Heymann D, Redini F. Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma-bearing mice. Cancer. 2005; 104:2522–2529. PMID: 16270320.

12. Lim JS, Hwang JS, Lee JA, Kim DH, Park KD, Cheon GJ, et al. Bone mineral density according to age, bone age, and pubertal stages in korean children and adolescents. J Clin Densitom. 2010; 13:68–76. PMID: 19942470.

13. Ruza E, Sierrasesúmaga L, Azcona C, Patino-Garcia A. Bone mineral density and bone metabolism in children treated for bone sarcomas. Pediatr Res. 2006; 59:866–871. PMID: 16641212.

14. Müller C, Winter CC, Rosenbaum D, Boos J, Gosheger G, Hardes J, et al. Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients. BMC Musculoskelet Disord. 2010; 11:287. PMID: 21190557.

15. Stanisavljevic S, Babcock AL. Fractures in children treated with methotrexate for leukemia. Clin Orthop Relat Res. 1977; (125):139–144. PMID: 880755.

16. Bonjour JP, Chevalley T. Pubertal timing, bone acquisition, and risk of fracture throughout life. Endocr Rev. 2014; 35:820–847. PMID: 25153348.

17. Cooper C, Westlake S, Harvey N, Javaid K, Dennison E, Hanson M. Review: developmental origins of osteoporotic fracture. Osteoporos Int. 2006; 17:337–347. PMID: 16331359.

18. Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998; 339:947–952. PMID: 9753709.

19. Shaw NJ, Boivin CM, Crabtree NJ. Intravenous pamidronate in juvenile osteoporosis. Arch Dis Child. 2000; 83:143–145. PMID: 10906023.

20. Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, Bachrach SJ. Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial. J Pediatr. 2002; 141:644–651. PMID: 12410192.

21. Cimaz R, Gattorno M, Sormani MP, Falcini F, Zulian F, Lepore L, et al. Changes in markers of bone turnover and inflammatory variables during alendronate therapy in pediatric patients with rheumatic diseases. J Rheumatol. 2002; 29:1786–1792. PMID: 12180745.

22. Nguyen T, Zacharin MR. Pamidronate treatment of steroid associated osteonecrosis in young patients treated for acute lymphoblastic leukaemia--two-year outcomes. J Pediatr Endocrinol Metab. 2006; 19:161–167. PMID: 16562590.

23. Meyers PA, Healey JH, Chou AJ, Wexler LH, Merola PR, Morris CD, et al. Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer. 2011; 117:1736–1744. PMID: 21472721.

24. Batch JA, Couper JJ, Rodda C, Cowell CT, Zacharin M. Use of bisphosphonate therapy for osteoporosis in childhood and adolescence. J Paediatr Child Health. 2003; 39:88–92. PMID: 12603794.

25. Gandrud LM, Cheung JC, Daniels MW, Bachrach LK. Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis. J Pediatr Endocrinol Metab. 2003; 16:887–892. PMID: 12948302.

26. Lee J, Yoon J, Lee YA, Lim JS, Shin CH, Yang SW. Pamidronate therapy in children and adolescents with secondary osteoporosis. J Korean Soc Pediatr Endocrinol. 2011; 16:178–184.

27. Bachrach LK, Ward LM. Clinical review 1: Bisphosphonate use in childhood osteoporosis. J Clin Endocrinol Metab. 2009; 94:400–409. PMID: 19033370.

28. Lajer H, Daugaard G. Cisplatin and hypomagnesemia. Cancer Treat Rev. 1999; 25:47–58. PMID: 10212589.

29. Reddy CR, Coburn JW, Hartenbower DL, Friedler RM, Brickman AS, Massry SG, et al. Studies on mechanisms of hypocalcemia of magnesium depletion. J Clin Invest. 1973; 52:3000–3010. PMID: 4750437.

30. Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007; (4):CD005324. PMID: 17943849.